The present invention is directed to fluid movement, and more specifically, to the movement of small drops of fluid through the use of acoustic waves.
A number of applications, such as combinatorial chemistry, high throughput screening, among others, include a procedure for taking small amounts of liquid reagents contained in a well plate, and then depositing the small amounts of reagents in different combinations into other well plates, i.e., a well-plate-to-well-plate transfer. An issue which arises in the transfer of fluids from well plate to well plate is potential contamination of the donor well plate. Particularly, the donor well plate may contain material which is part of a library of donor materials that can number in the millions of compounds and represent a major investment for an institution, corporation or other organization.
Presently, these compounds are often transferred by an exchange apparatus using disposable tips. The exchange apparatus may be a vacuum pipette system, wherein the tip comes into contact with fluids in wells of the donor well plate. Therefore, after each operation the disposable tip is replaced with a new tip, such that the next time the pipette is used, contamination will not occur when the pipette is placed into a different well in the donor well plate.
The need to replace the disposable tip has certain drawbacks, including slowing down the transfer process, and the financial cost of tip replacement. A further drawback is that the reagent maintained in the tip is discarded with the tip. Commonly, the reagent and/or other fluids in the well plates are themselves expensive, and such waste of these materials adds to the economic cost of the transfer.
In order to minimize, and more desirably eliminate, contamination issues, it is considered useful to employ a transfer mechanism or procedure to remove droplets from the donor well plate without physical contact to the fluid.
In U.S. Pat. No. 6,416,164 to Stearns, et al., a transfer mechanism is taught to be eject fluids from a well plate without physical contact, and further to use this transfer mechanism for well-plate-to-well-plate transfer. The '164 patent is hereby incorporated by reference in its entirety. In that patent, an acoustic ejector, including a focusing element and acoustic radiation generator imparts an acoustic wave through the bottom surface of a well to eject droplets from a well plate. It is argued in this patent, that prior devices employed lensing designs which did not permit for the projecting of a focal point far enough into a well to emit acoustic droplets.
More particularly, for example, it was noted that the base of a Greiner 1536 well has an extent of approximately 1.53 mm. The narrowness of this well limits the physical dimension of the acoustic beam which may enter a column of liquid contained within the well, as acoustic beams that are wider than the base of the well would result in unwanted generation of complex pattern of refraction in the well walls. The height of the walls in such a well is 5 mm, more than three times the dimension of the base. Using an F1 lens and maintaining the extent of the acoustic energy within the well base, the depth from which the lens could effect ejection would be substantially under 2 mm. Hence, it was argued the fluid could not be ejected from such a well if the well was more than half full. The patent noted that in contrast, by using a weakly focusing lens such as an F3 lens, the full height of the liquid would be within the range of focus.
Thus, patent is concerned with ejecting droplets from a container having a greater depth than width ratio, when the acoustic waves being used to eject droplets enter the reservoir from the bottom of the reservoir.
It has been determined by the inventors that an alternative method and design for emitting or obtaining drops from a fluid reservoir such as a well plate would be useful, where contamination of the fluid within the well plates is avoided.